Sex-Specific Differences in the Secretome of Oligodendrocyte Progenitor Cells Post Hyperoxic Stress

Abstract

Cerebral oxygenation differences in the neonatal period of human preterm infants, along with sex-specific differences in combating oxidative stress, can lead to disruption of normal oligodendrocyte maturation and function, which in turn can differentially affect neuronal development and activity in the male and female brains. Secretory proteins and extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication and stress response in the brain. Our analysis of the secretome from cell culture supernatants obtained after treating male and female derived primary mouse OPCs with hyperoxia (80% O₂) for a 24 h period showed prominent sex-specific protein signatures with only 6% intersection between sexes upon hyperoxia. A higher proportion of mitochondrial proteins was observed to be secreted by male cells upon hyperoxic stress. Among specific factors that could be identified exclusively in the hyperoxia-treated groups, FGF-2 was present in significantly higher amounts in the female supernatant. Functional assays on neuronal cells (male) revealed that treatment with supernatant from female hyperoxic OPCs resulted in increased neuronal viability, potentially due to elevated levels of FGF-2. This suggests that female-specific extracellular proteins may play a key role in sex specific stress response and are potential candidates for further investigation.